Ozonolysis of ketoprofen in polluted water: Reaction pathways, kinetics, removal efficiency, and health effects.

Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.

DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korean Health Insurance Review and Assessment Service database.

DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA.

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

Purpose: The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. Methods: IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Results: Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 µM. Conclusion: We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE: A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS: Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS: A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION: GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Risks of dairy derived excipients in medications for lactose intolerant and cow milk protein allergic patients.

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.

Dietary Walnuts Prevented Indomethacin-Induced Gastric Damage via AP-1 Transcribed 15-PGDH, Nrf2-Mediated HO-1, and n-3 PUFA-Derived Resolvin E1.

Non-steroidal anti-inflammatory drugs (NSAIDs), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, cause gastric mucosal damage, including ulcers, directly or indirectly, by which the development of GI-safer (-sparing) NSAIDs relates to unmet medical needs. This study aimed to document the preventive effects of walnut polyphenol extracts (WPEs) against NSAID-induced gastric damage along with the molecular mechanisms. RGM-1 gastric mucosal cells were administered with indomethacin, and the expressions of the inflammatory mediators between indomethacin alone or a combination with WPEs were compared. The expressions of the inflammatory mediators, including COX-1 and COX-2, prostaglandin E2, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and antioxidant capacity, were analyzed by Western blot analysis, RT-PCR, and ELISA, respectively. HO-1, Nrf-2, and keap1 were investigated. The in vivo animal models were followed with in vitro investigations. The NSAIDs increased the expression of COX-2 and decreased COX-1 and 15-PGDH, but the WPEs significantly attenuated the NSAID-induced COX-2 expression. Interestingly, the WPEs induced the expression of 15-PGDH. By using the deletion constructs of the 15-PGDH promoter, we found that c-Jun is the most essential determinant of the WPE-induced up-regulation of 15-PGDH expression. We confirmed that the knockdown of c-Jun abolished the ability of the WPEs to up-regulate the 15-PGDH expression. In addition, the WPEs significantly increased the HO-1 expression. The WPEs increased the nuclear translocation of Nrf2 by Keap-1 degradation, and silencing Nrf2 markedly reduced the WPE-induced HO-1 expression. We found that the WPE-induced HO-1 up-regulation was attenuated in the cells harboring the mutant Keap1, in which the cysteine 151 residue was replaced by serine. These in vitro findings were exactly validated in indomethacin-induced gastric rat models. Daily walnut intake can be a promising nutritional supplement providing potent anti-inflammatory, antioxidative, and mucosa-protective effects against NSAID-induced GI damage.

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Revisiting and Updating the Interaction between Human Serum Albumin and the Non-Steroidal Anti-Inflammatory Drugs Ketoprofen and Ketorolac.

Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

Chondrotoxicity of Intra-Articular Injection Treatment: A Scoping Review.

The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Activity of apremilast in a patient with severe pemphigus vulgaris: case report.

Introduction: Although the treatment for pemphigus vulgaris (PV) has been revolutionized by the use of rituximab combined with corticosteroids, new effective therapies with a better safety profile are needed. Observation: A 67-year-old woman was diagnosed with severe mucosal PV, which was initially misdiagnosed as atypical Behçet's disease. Following an unsuccessful colchicine treatment, significant improvement was observed upon the introduction of apremilast: reduced pain, fewer lesions, and a stabilized weight. The discontinuation of apremilast led to a rapid relapse. Retrospective analysis through anti-Dsg3 ELISA indicated a gradual decrease in antibody levels during the apremilast treatment. Discussion: Apremilast, a phosphodiesterase 4 inhibitor approved for psoriasis and Behçet's disease's related oral ulcers treatment, demonstrated its efficacy in this PV case. This is the second case report highlighting the effectiveness of apremilast for PV treatment. Apremilast's ability to upregulate cyclic adenosine monophosphate (cAMP) levels appears to contribute to the stabilization of keratinocyte adhesion. Conclusion: Apremilast may be a promising therapeutic option for the treatment of pemphigus, with an innovative mechanism of action, no induced immunosuppression, and good tolerance. It could be a good alternative to steroids, in the treatment regimen of steroids combined with rituximab.

Gout: A Rapid Review of Presentation, Diagnosis and Management.

Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.

Nonsteroidal Anti-Inflammatory Drugs and Experimental Chagas Disease: An Unsolved Question.

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti-inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding.

THE IMPACT OF SYSTEMIC DRUGS ON DENTAL IMPLANT OSSEOINTEGRATION: A REVIEW.

The process of osteointegration of dental implants is a biological process. Systemic therapy can interfere with this process, affecting the growth and breakdown processes of the bone and ultimately leading to implant failure. This literature review focuses on specific groups of systemic drugs that directly impact osteointegration. The research in electronic literature was conducted using the National Library of Medicine's PubMed/MEDLINE database from March 2000 to February 2024. The following MeSH (Medical Subject Headings) terms were used: "implant osseointegration," "bisphosphonates," "non-steroidal anti-inflammatory drugs," "glucocorticoids," "proton pump inhibitors," and "selective serotonin reuptake inhibitors (SSRIs)." This search yielded 1,258 articles on implant osseointegration. Among these, 30 articles met our criteria for implant osseointegration and bisphosphonates, 2 articles for non-steroidal anti-inflammatory drugs (NSAIDs), 7 articles for glucocorticoids, 14 articles for proton pump inhibitors (PPIs), and 14 articles for selective serotonin reuptake inhibitors (SSRIs). Clinicians considering implant therapy should be mindful of potential medication-related implant failures. The present systematic review has identified an association between proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), glucocorticoids, and bisphosphonates with an increased implant failure rate.

Pirfenidone use in fibrotic diseases: What do we know so far?

BACKGROUND: Pirfenidone has demonstrated significant anti-inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti-inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro-inflammatory cytokines, apoptosis, and fibroblast activation. OBJECTIVE: To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. FINDINGS: Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. CONCLUSION: Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions.

Nonsurgical therapy for lumbar spinal stenosis caused by ligamentum flavum hypertrophy: A review.

Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH.

The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: A promising therapeutic compound against the cytokine storm.

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 µM, 95% CI = 7.4 to 10.4 µM) was comparable to that of paracetamol (IC50 = 7.73 µM, 95% CI = 6.14 to 9.73 µM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.

Pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid in rainbow trout (Oncorhynchus mykiss).

BACKGROUND: Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties. OBJECTIVES: The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C. METHODS: The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis. RESULTS: The elimination half-life (t1/2ʎz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent. CONCLUSIONS: While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.

A rare case of meloxicam-induced pseudoporphyria.

Drug-induced pseudoporphyria is commonly linked to nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, oxaprozin, ketoprofen, and ibuprofen. The NSAID meloxicam is not a commonly reported inciting agent. We report a case of meloxicam-induced pseudoporphyria in a 55-year-old woman with a past medical history of hypertension, hyperlipidemia, gastroesophageal reflux disease, and osteoarthritis. She presented to the clinic with tense and denuded bullae on her dorsal feet, which was diagnosed as pseudoporphyria after further workup. Upon evaluating the patient's medication history, meloxicam was identified as the most likely inciting agent. The patient's condition resolved with the discontinuation of this medication. Our findings can help dermatologists effectively diagnose and treat meloxicam-induced pseudoporphyria in patients with similar cases.